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# TODO: check
# *** Open Babel Error in ParseFile
# Could not find contribution data file.
CACTUS_URI="http://cactus.nci.nih.gov/chemical/structure/"
module OpenTox
class Compound
require_relative "unique_descriptors.rb"
include OpenTox
include OpenTox::Descriptor
DEFAULT_FINGERPRINT = "MP2D"
field :inchi, type: String
field :smiles, type: String
field :inchikey, type: String
field :names, type: Array
#field :warnings, type: Array, default: []
field :cid, type: String
field :chemblid, type: String
field :png_id, type: BSON::ObjectId
field :svg_id, type: BSON::ObjectId
field :sdf_id, type: BSON::ObjectId
field :molecular_weight, type: Float
field :fingerprints, type: Hash, default: {}
field :default_fingerprint_size, type: Integer
field :physchem_descriptors, type: Hash, default: {}
field :dataset_ids, type: Array, default: []
field :features, type: Hash, default: {}
index({smiles: 1}, {unique: true})
#index({default_fingerprint: 1}, {unique: false})
# Overwrites standard Mongoid method to create fingerprints before database insertion
def self.find_or_create_by params
compound = self.find_or_initialize_by params
compound.default_fingerprint_size = compound.fingerprint(DEFAULT_FINGERPRINT).size
compound.save
compound
end
def fingerprint type=DEFAULT_FINGERPRINT
unless fingerprints[type]
return [] unless self.smiles
#http://openbabel.org/docs/dev/FileFormats/MolPrint2D_format.html#molprint2d-format
if type == "MP2D"
fp = obconversion(smiles,"smi","mpd").strip.split("\t")
name = fp.shift # remove Title
fingerprints[type] = fp.uniq # no fingerprint counts
#http://openbabel.org/docs/dev/FileFormats/Multilevel_Neighborhoods_of_Atoms_(MNA).html
elsif type== "MNA"
level = 2 # TODO: level as parameter, evaluate level 1, see paper
fp = obconversion(smiles,"smi","mna","xL\"#{level}\"").split("\n")
fp.shift # remove Title
fingerprints[type] = fp
else # standard fingerprints
fp = OpenBabel::OBFingerprint.find_fingerprint(type)
obmol = OpenBabel::OBMol.new
obconversion = OpenBabel::OBConversion.new
obconversion.set_in_format "smi"
obconversion.read_string obmol, self.smiles
result = OpenBabel::VectorUnsignedInt.new
fp.get_fingerprint(obmol,result)
# TODO: %ignore *::DescribeBits @ line 163 openbabel/scripts/openbabel-ruby.i
#p OpenBabel::OBFingerprint.describe_bits(result)
# convert result to a list of the bits that are set
# from openbabel/scripts/python/pybel.py line 830
# see also http://openbabel.org/docs/dev/UseTheLibrary/Python_Pybel.html#fingerprints
result = result.to_a
bitsperint = OpenBabel::OBFingerprint.getbitsperint()
bits_set = []
start = 1
result.each do |x|
i = start
while x > 0 do
bits_set << i if (x % 2) == 1
x >>= 1
i += 1
end
start += bitsperint
end
fingerprints[type] = bits_set
end
save
end
fingerprints[type]
end
def physchem descriptor_ids
calculated_descriptor_ids = self[:physchem_descriptors].keys
p names
new = UNIQUEDESCRIPTORS-names
p new
d = self.physchem(self, new)
#p d
#self[:physchem_descriptors].merge! d
self.update_attribute(:physchem_descriptors, self[:physchem_descriptors].merge(d))
save
self[:physchem_descriptors]
end
# Create a compound from smiles string
# @example
# compound = OpenTox::Compound.from_smiles("c1ccccc1")
# @param [String] smiles Smiles string
# @return [OpenTox::Compound] Compound
def self.from_smiles smiles
if smiles.match(/\s/) # spaces seem to confuse obconversion and may lead to invalid smiles
$logger.warn "SMILES parsing failed for '#{smiles}'', SMILES string contains whitespaces."
return nil
end
smiles = obconversion(smiles,"smi","can") # test if SMILES is correct and return canonical smiles (for compound comparisons)
if smiles.empty?
$logger.warn "SMILES parsing failed for '#{smiles}'', this may be caused by an incorrect SMILES string."
return nil
else
Compound.find_or_create_by :smiles => smiles
end
end
# Create a compound from inchi string
# @param inchi [String] smiles InChI string
# @return [OpenTox::Compound] Compound
def self.from_inchi inchi
# Temporary workaround for OpenBabels Inchi bug
# http://sourceforge.net/p/openbabel/bugs/957/
# bug has not been fixed in latest git/development version
#smiles = `echo "#{inchi}" | "#{File.join(File.dirname(__FILE__),"..","openbabel","bin","babel")}" -iinchi - -ocan`.chomp.strip
smiles = obconversion(inchi,"inchi","can")
if smiles.empty?
Compound.find_or_create_by(:warnings => ["InChi parsing failed for #{inchi}, this may be caused by an incorrect InChi string or a bug in OpenBabel libraries."])
else
Compound.find_or_create_by(:smiles => smiles, :inchi => inchi)
end
end
# Create a compound from sdf string
# @param sdf [String] smiles SDF string
# @return [OpenTox::Compound] Compound
def self.from_sdf sdf
# do not store sdf because it might be 2D
Compound.from_smiles obconversion(sdf,"sdf","can")
end
# Create a compound from name. Relies on an external service for name lookups.
# @example
# compound = OpenTox::Compound.from_name("Benzene")
# @param name [String] can be also an InChI/InChiKey, CAS number, etc
# @return [OpenTox::Compound] Compound
def self.from_name name
Compound.from_smiles RestClientWrapper.get(File.join(CACTUS_URI,URI.escape(name),"smiles"))
end
# Get InChI
# @return [String] InChI string
def inchi
unless self["inchi"]
result = obconversion(smiles,"smi","inchi")
#result = `echo "#{self.smiles}" | "#{File.join(File.dirname(__FILE__),"..","openbabel","bin","babel")}" -ismi - -oinchi`.chomp
update(:inchi => result.chomp) if result and !result.empty?
end
self["inchi"]
end
# Get InChIKey
# @return [String] InChIKey string
def inchikey
update(:inchikey => obconversion(smiles,"smi","inchikey")) unless self["inchikey"]
self["inchikey"]
end
# Get (canonical) smiles
# @return [String] Smiles string
def smiles
update(:smiles => obconversion(self["smiles"],"smi","can")) unless self["smiles"]
self["smiles"]
end
# Get sdf
# @return [String] SDF string
def sdf
if self.sdf_id.nil?
sdf = obconversion(smiles,"smi","sdf")
file = Mongo::Grid::File.new(sdf, :filename => "#{id}.sdf",:content_type => "chemical/x-mdl-sdfile")
sdf_id = $gridfs.insert_one file
update :sdf_id => sdf_id
end
$gridfs.find_one(_id: self.sdf_id).data
end
# Get SVG image
# @return [image/svg] Image data
def svg
if self.svg_id.nil?
svg = obconversion(smiles,"smi","svg")
file = Mongo::Grid::File.new(svg, :filename => "#{id}.svg", :content_type => "image/svg")
update(:svg_id => $gridfs.insert_one(file))
end
$gridfs.find_one(_id: self.svg_id).data
end
# Get png image
# @example
# image = compound.png
# @return [image/png] Image data
def png
if self.png_id.nil?
png = obconversion(smiles,"smi","_png2")
file = Mongo::Grid::File.new(Base64.encode64(png), :filename => "#{id}.png", :content_type => "image/png")
update(:png_id => $gridfs.insert_one(file))
end
Base64.decode64($gridfs.find_one(_id: self.png_id).data)
end
# Get all known compound names. Relies on an external service for name lookups.
# @example
# names = compound.names
# @return [String] Compound names
def names
update(:names => RestClientWrapper.get("#{CACTUS_URI}#{inchi}/names").split("\n")) unless self["names"]
self["names"]
end
# @return [String] PubChem Compound Identifier (CID), derieved via restcall to pubchem
def cid
pug_uri = "http://pubchem.ncbi.nlm.nih.gov/rest/pug/"
update(:cid => RestClientWrapper.post(File.join(pug_uri, "compound", "inchi", "cids", "TXT"),{:inchi => inchi}).strip) unless self["cid"]
self["cid"]
end
# @return [String] ChEMBL database compound id, derieved via restcall to chembl
def chemblid
# https://www.ebi.ac.uk/chembldb/ws#individualCompoundByInChiKey
uri = "http://www.ebi.ac.uk/chemblws/compounds/smiles/#{smiles}.json"
update(:chemblid => JSON.parse(RestClientWrapper.get(uri))["compounds"].first["chemblId"]) unless self["chemblid"]
self["chemblid"]
end
def fingerprint_count_neighbors params
# TODO fix
neighbors = []
query_fingerprint = self.fingerprint params[:type]
training_dataset = Dataset.find(params[:training_dataset_id]).compounds.each do |compound|
unless self == compound
candidate_fingerprint = compound.fingerprint params[:type]
features = (query_fingerprint + candidate_fingerprint).uniq
min_sum = 0
max_sum = 0
features.each do |f|
min,max = [query_fingerprint.count(f),candidate_fingerprint.count(f)].minmax
min_sum += min
max_sum += max
end
max_sum == 0 ? sim = 0 : sim = min_sum/max_sum.to_f
neighbors << [compound.id, sim] if sim and sim >= params[:min_sim]
end
end
neighbors.sort{|a,b| b.last <=> a.last}
end
def fingerprint_neighbors params
bad_request_error "Incorrect parameters '#{params}' for Compound#fingerprint_neighbors. Please provide :type, :training_dataset_id, :min_sim." unless params[:type] and params[:training_dataset_id] and params[:min_sim]
neighbors = []
if params[:type] == DEFAULT_FINGERPRINT
neighbors = db_neighbors params
else
query_fingerprint = self.fingerprint params[:type]
training_dataset = Dataset.find(params[:training_dataset_id])
prediction_feature = training_dataset.features.first
training_dataset.compounds.each do |compound|
#unless self == compound
candidate_fingerprint = compound.fingerprint params[:type]
sim = (query_fingerprint & candidate_fingerprint).size/(query_fingerprint | candidate_fingerprint).size.to_f
feature_values = training_dataset.values(compound,prediction_feature)
neighbors << {"_id" => compound.id, "features" => {prediction_feature.id.to_s => feature_values}, "tanimoto" => sim} if sim >= params[:min_sim]
#end
end
neighbors.sort!{|a,b| b["tanimoto"] <=> a["tanimoto"]}
end
neighbors
end
def fminer_neighbors params
bad_request_error "Incorrect parameters for Compound#fminer_neighbors. Please provide :feature_dataset_id, :min_sim." unless params[:feature_dataset_id] and params[:min_sim]
feature_dataset = Dataset.find params[:feature_dataset_id]
query_fingerprint = Algorithm::Descriptor.smarts_match(self, feature_dataset.features)
neighbors = []
# find neighbors
feature_dataset.data_entries.each_with_index do |candidate_fingerprint, i|
sim = Algorithm::Similarity.tanimoto candidate_fingerprint, query_fingerprint
if sim >= params[:min_sim]
neighbors << [feature_dataset.compound_ids[i],sim] # use compound_ids, instantiation of Compounds is too time consuming
end
end
neighbors
end
def physchem_neighbors params
feature_dataset = Dataset.find params[:feature_dataset_id]
query_fingerprint = Algorithm.run params[:feature_calculation_algorithm], self, params[:descriptors]
neighbors = []
feature_dataset.data_entries.each_with_index do |candidate_fingerprint, i|
# TODO implement pearson and cosine similarity separatly
R.assign "x", query_fingerprint
R.assign "y", candidate_fingerprint
# pearson r
#sim = R.eval("cor(x,y,use='complete.obs',method='pearson')").to_ruby
#p "pearson"
#p sim
#p "cosine"
sim = R.eval("x %*% y / sqrt(x%*%x * y%*%y)").to_ruby.first
#p sim
if sim >= params[:min_sim]
neighbors << [feature_dataset.compound_ids[i],sim] # use compound_ids, instantiation of Compounds is too time consuming
end
end
neighbors
end
def db_neighbors params
# from http://blog.matt-swain.com/post/87093745652/chemical-similarity-search-in-mongodb
#qn = default_fingerprint_size
#qmin = qn * threshold
#qmax = qn / threshold
#not sure if it is worth the effort of keeping feature counts up to date (compound deletions, additions, ...)
#reqbits = [count['_id'] for count in db.mfp_counts.find({'_id': {'$in': qfp}}).sort('count', 1).limit(qn - qmin + 1)]
aggregate = [
#{'$match': {'mfp.count': {'$gte': qmin, '$lte': qmax}, 'mfp.bits': {'$in': reqbits}}},
#{'$match' => {'_id' => {'$ne' => self.id}}}, # remove self
{'$project' => {
'tanimoto' => {'$let' => {
'vars' => {'common' => {'$size' => {'$setIntersection' => ["$fingerprints.#{DEFAULT_FINGERPRINT}", fingerprints[DEFAULT_FINGERPRINT]]}}},
#'vars' => {'common' => {'$size' => {'$setIntersection' => ["$default_fingerprint", default_fingerprint]}}},
'in' => {'$divide' => ['$$common', {'$subtract' => [{'$add' => [default_fingerprint_size, '$default_fingerprint_size']}, '$$common']}]}
}},
'_id' => 1,
'features' => 1,
'dataset_ids' => 1
}},
{'$match' => {'tanimoto' => {'$gte' => params[:min_sim]}}},
{'$sort' => {'tanimoto' => -1}}
]
$mongo["compounds"].aggregate(aggregate).select{|r| r["dataset_ids"].include? params[:training_dataset_id]}
#$mongo["compounds"].aggregate(aggregate).collect{ |r| [r["_id"], r["tanimoto"]] }
end
# Convert mg to mmol
# @return [Float] value in mg
def mmol_to_mg mmol
mmol.to_f*molecular_weight
end
# Convert mmol to mg
# @return [Float] value in mg
def mg_to_mmol mg
mg.to_f/molecular_weight
end
# Calculate molecular weight of Compound with OB and store it in object
# @return [Float] molecular weight
def molecular_weight
if self["molecular_weight"]==0.0 || self["molecular_weight"].nil?
update(:molecular_weight => OpenTox::Algorithm::Descriptor.physchem(self, ["Openbabel.MW"]).first)
end
self["molecular_weight"].to_f
end
private
def self.obconversion(identifier,input_format,output_format,option=nil)
obconversion = OpenBabel::OBConversion.new
obconversion.set_options(option, OpenBabel::OBConversion::OUTOPTIONS) if option
obmol = OpenBabel::OBMol.new
obconversion.set_in_and_out_formats input_format, output_format
return nil if identifier.nil?
obconversion.read_string obmol, identifier
case output_format
when /smi|can|inchi/
obconversion.write_string(obmol).gsub(/\s/,'').chomp
when /sdf/
# TODO: find disconnected structures
# strip_salts
# separate
obmol.add_hydrogens
builder = OpenBabel::OBBuilder.new
builder.build(obmol)
sdf = obconversion.write_string(obmol)
print sdf
if sdf.match(/.nan/)
$logger.warn "3D generation failed for compound #{identifier}, trying to calculate 2D structure"
obconversion.set_options("gen2D", OpenBabel::OBConversion::GENOPTIONS)
sdf = obconversion.write_string(obmol)
if sdf.match(/.nan/)
$logger.warn "2D generation failed for compound #{identifier}, rendering without coordinates."
obconversion.remove_option("gen2D", OpenBabel::OBConversion::GENOPTIONS)
sdf = obconversion.write_string(obmol)
end
end
sdf
else
obconversion.write_string(obmol)
end
end
def obconversion(identifier,input_format,output_format,option=nil)
self.class.obconversion(identifier,input_format,output_format,option)
end
end
end
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